Vascular endothelial growth factors and angiopoietins as new players in mastocytosis

• Published in: Clinical and experimental medicine 2021-08, Vol.21 (3), p.415-427
• Main Authors: Marcella, Simone, Petraroli, Angelica, Braile, Mariantonia, Parente, Roberta, Ferrara, Anne Lise, Galdiero, Maria Rosaria, Modestino, Luca, Cristinziano, Leonardo, Rossi, Francesca Wanda, Varricchi, Gilda, Triggiani, Massimo, de Paulis, Amato, Spadaro, Giuseppe, Loffredo, Stefania
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Angiopoietins - blood; Case-Control Studies; Cell Line; Cell lines; Cell proliferation; Female; Gain of Function Mutation; Growth factors; Hematology; Humans; Internal Medicine; Male; Mast cells; Mastocytosis; Mastocytosis - blood; Mastocytosis - genetics; Mastocytosis - metabolism; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original; Original Article; Patient Acuity; Patients; Proto-Oncogene Proteins c-kit - genetics; Retrospective Studies; Tryptase; Up-Regulation; Vascular endothelial growth factor; Vascular Endothelial Growth Factors - blood; Young Adult
• ISSN: 1591-8890; 1591-9528
• DOI: 10.1007/s10238-021-00693-0

Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. MCs produce angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (ANGPTs). Serum concentrations of VEGF-A, VEGF-C, VEGF-D, ANGPT1 and ANGPT2 were determined in 64 mastocytosis patients and 64 healthy controls. Intracellular concentrations and spontaneous release of these mediators were evaluated in the mast cell lines ROSA KIT WT and ROSA KIT D816V and in human lung mast cells (HLMCs). VEGF-A, ANGPT1, ANGPT2 and VEGF-C concentrations were higher in mastocytosis patients compared to controls. The VEGF-A, ANGPT2 and VEGF-C concentrations were correlated with the symptom severity. ANGPT1 concentrations were increased in all patients compared to controls. ANGPT2 levels were correlated with severity of clinical variants and with tryptase levels. VEGF-A, ANGPT1 and VEGF-C did not differ between indolent and advanced mastocytosis. ROSA KIT WT , ROSA KIT D816V and HLMCs contained and spontaneously released VEGFs and ANGPTs. Serum concentrations of VEGFs and ANGPTs are altered in mastocytosis patients.